Durable responses in metastatic cancers have been obtained with a variety of immunotherapies such as interleukin-2 (IL-2), tumor-infiltrating lymphocyte (TIL) adoptive cell transfer therapy, cytotoxic T lymphocyte antigen-4 (CTLA4) blocking antibodies1-5 and with programmed death 1 (PD-1) blocking antibodies6-10. Approximately 75% of objective responses to anti-programmed death (PD-1) therapy are durable, lasting years but delayed relapses have been noted long after an initial objective tumor regression while on continuous therapy. Approximately 25% of patients with an objective response to PD-1 blockade therapy in melanoma developed progression with a median follow up of 21 months11. Mechanisms of immune escape in this setting have remained unknown.